What question did this study set out to answer?

To evaluate the impact of tumor-infiltrating clonal hematopoiesis on overall survival and progression risk in advanced non-small cell lung cancer.

March 21, 2026ESMO Open0 citationsOpen Access

131P Clinical impact of tumor-infiltrating clonal hematopoiesis of indeterminate potential (TI-CHIP) in advanced non-small cell lung cancer (NSCLC)

AVA. VitaleAgostino Gemelli University Polyclinic EPE. De PaolisAgostino Gemelli University Polyclinic ASAlessio StefaniAgostino Gemelli University Polyclinic

Key Points

To evaluate the impact of tumor-infiltrating clonal hematopoiesis on overall survival and progression risk in advanced non-small cell lung cancer.
Analyzed overall survival (OS) and progression-free survival (WFFS) in relation to tumor-infiltrating clonal hematopoiesis and organ involvement.
Defined low-risk versus high-risk progression groups based on DMV (dynamic molecular variations) and organ involvement.
Assessed genomic alterations associated with higher DMV including EZH2 and MYC.
Patients with low-risk progression had significantly longer OS (22.0 vs 10.3 months, p=0.0013).
Higher DMV was linked to specific genomic alterations, such as EZH2 and MYC enrichment (9% vs 0%).
Increased alterations in the NRF2 pathway were observed in high DMV cases (27% vs 9%, p=0.04).

Abstract

4 months; p=0.038) and a trend toward improved OS (17.1 vs 10.2 months; p=0.055).Multiple-organ involvement was associated with inferior OS (median 10.3 vs 22.0 months; p=0.001) and WFFS (7.4 vs 15.8 months; p=0.004).A low-risk progression group defined by lower DMV and single-organ involvement demonstrated significantly longer OS (22.0 vs 10.3 months; p=0.0013) and WFFS (15.8 vs 7.4 months; p=0.0035) vs high-risk progression.Higher DMV was associated with enrichment of EZH2 (9% vs 0%) and MYC alterations (9% vs 0%), increased NRF2 pathway alterations (27% vs 9%; p=0.04).Conclusions: DMV and a simple progression risk score integrating DMV and organ involvement provide quantitative prognostic stratification after oligometastatic progression in NSCLC.Distinct genomic correlates associated with higher DMV suggest underlying biological drivers of metastatic trajectories.These accessible metrics may support patient selection for local therapy and prospective trial stratification.

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